细胞自噬与人卵巢癌细胞对顺铂耐药的关系  

Cell autophagy promotes ovarian cancer cells resistance to Cisplatin

作　　者：朱星枚[1,2] 吴琳[3] 张媛[3] 姚杨[1] 成碧萍 张丹[2] 

机构地区：[1]西安医学院第一附属医院中心实验室,陕西西安710077 [2]陕西中医药大学中药化学教研室,陕西西咸新区712046 [3]第四军医大学生物化学与分子生物学教研室,陕西西安710032

出　　处：《中国医药导报》2016年第25期12-16,共5页China Medical Herald

基　　金：陕西省教育厅专项科研计划项目(14JK1633);陕西省自然科学基础研究计划项目(2013JC2-21);陕西中医药大学校级基金项目(2015QN18)

摘　　要：目的探讨细胞自噬与人卵巢癌细胞对顺铂耐药的关系。方法以不同浓度的顺铂(0、1、2、4、8、16μg/mL)分别作用人卵巢癌细胞A2780及其顺铂耐药株A2780/DDP 48h,采用MTT法检测卵巢癌细胞的增殖率,透射电镜检测顺铂诱导细胞自噬体的形成,Western blot法测定自噬和凋亡相关蛋白。结果与A2780对照比较,A2780/DDP增殖率明显升高(P<0.01);顺铂可以诱导A2780及A2780/DDP中自噬体的形成,且A2780和A2780/DDP中LC3-Ⅱ水平均升高,这种作用可以被自噬抑制剂3-甲基腺嘌呤(3-MA)阻断;顺铂可以诱导A2780中凋亡相关蛋白Cleaved-PARP水平升高,但作用A2780/DDP时影响不大,当3-MA与顺铂同时作用人卵巢癌细胞时,A2780/DDP中的Cleaved-PARP表达水平显著升高(P<0.01)。结论卵巢癌细胞的耐药可能与顺铂诱导卵巢癌细胞自噬有关,自噬抑制剂3-MA可以抑制顺铂诱导的细胞自噬,同时促进顺铂诱导人卵巢癌细胞凋亡,且增加顺铂耐药株对顺铂的敏感性。Objective To study the relationship between cell autophagy and Cisplatin resistance in the ovarian cancer ceils. Methods Cell proliferation was determined by an MTT assay after A2780 and A2780/DDP cells were treated by Cisplatin at different concentrations （0, 1, 2, 4, 8, 16 μg/mL） for 48 h, the formation of autophagosomes were detected by transmission electron microscopy, both autophagy and apoptosis related protein expression were determined by Western blot. Results Compared with the control of A2780, A2780/DDP proliferation rate was significantly increased （P 〈 0.01）; Autophagy, characterized by an increase in the number of autophagosomes and LC3-II protein level, was observed in Cisplatin-treated A2780 and Cisplatin-treated A2780/DDP cells, which could be blocked by aatophagy in- hibitor 3-methyl adenine （3-MA）; Cleaved-PARP protein level was increased in Cisplatin-treated A2780 ceils while almost no effect in Cisplatin-treated A2780/DDP cells, however, Cleaved-PARP protein level was significantly increased in Cispiatin and 3-MA-treated A2780/DDP cells （P 〈 0.01）. Conclusion Resistance of ovarian cancer cells may be associated with autophagy induced by Cisplatin, autophagy inhibitor 3-MA can inhibite autophagy, but promote apoptosis induced by Cisplatin in ovarian cancer cells, and increase the Cisplatin sensitivity to Cisplatin resistant strains.

关 键 词：顺铂 耐药 卵巢癌 增殖 细胞自噬 凋亡 

分 类 号：R965[医药卫生—药理学]